A novel, optical detection system for detecting conformational change in a GPCR (G Protein-coupled receptor) has been devised. The detection system is based on second-harmonic generation, a nonlinear optical technique. Phase I specific aims are final construction, control experiments and optimization to demonstrate feasibility of the detection system. The beta-2 adrenergic receptor, a prototypical GPCR, will be the model protein for Phase I studies. Drug screening and basic scientific studies of receptor activation are the long-term objectives of the proposed detection system. [unreadable] [unreadable]